Regional Patterns of Decreased Grey-Matter Volume are Associated with Non-Response to Temporary CSF Drainage in iNPH

INTRODUCTION: Temporary drainage of cerebrospinal fluid (CSF) by lumbar puncture or lumbar drain has a high predictive value for identifying patients with idiopathic normal pressure hydrocephalus (iNPH) who will benefit from shunt insertion. However, it is unclear what differentiates responders from non-responders. One hypothesis is that there are patterns of reduced grey-matter volume (GMV) that predispose patients to a poor response. METHODS: Subjects included 132 patients with iNPH who underwent testing with temporary CSF drainage and who had undergone structural MRI between 2013 and 2021. Subjects were classified as responders or non-responders to temporary CSF drainage based on clinical examination and standardized measures of cognition (MoCA) and gait velocity. Demographic and clinical variables were examined between groups. Group differences in GMV were assessed using VBM while adjusting for age, sex, and total intracranial volume. RESULTS: There were 87 responders and 45 non-responders. There were no differences in age, sex, baseline gait velocity, CSF volume, or white-matter T2 hyperintensity volume. Non-responders had higher baseline MoCA scores and were more likely to have received lumbar puncture vs extended lumbar drainage. Responders had greater increases in MoCA and gait velocity scores. Non-responders demonstrated decreased GMV in the right supplementary motor area and in the right posterior parietal cortex as compared to responders. CONCLUSIONS: Decreased GMV in the supplementary motor area and posterior parietal cortex may identify patients with suspected iNPH likely to experience a negative response following temporary CSF drainage. These patients may have limited capacity for recovery due to atrophy in these regions known to be important for motor and cognitive integration.